Enantioselective mechanistic aspects

Fueled by the success of the Mn (salen) catalysts, new forays have been launched into the realm of hybrid catalyst systems. For example, the Mn-picolinamide-salicylidene complexes (i.e., 13) represent novel oxidation-resistant catalysts which exhibit higher turnover rates than the corresponding Jacobsen-type catalysts. These hybrids are particularly well-suited to the low-cost-but relatively aggressive-oxidant systems, such as bleach. In fact, the epoxidation of trans-P-methylstyrene (14) in the presence of 5 mol% of catalyst 13 and an excess of sodium hypochlorite proceeds with an ee of 53%. Understanding of the mechanistic aspects of these catalysts is complicated by their lack of C2 symmetry. For example, it is not yet clear whether the 5-membered or 6-membered metallocycle plays the decisive role in enantioselectivity however, in any event, the active form is believed to be a manganese 0x0 complex <96TL2725>. 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

In recent years the synthetic potential and mechanistic aspects of asymmetric catalysis with chiral Lewis base have been investigated. Aldol addition reactions between trichlorosilyl enolates with aldehydes have been also intensively studied. Now, full investigations of the trichlorosilyl enolates derived from achiral and chiral methyl ketones, in both uncatalysed and catalysed reactions with chiral and achiral aldehyde acceptors have been reported. The aldol addition is dramatically accelerated by the addition of chiral phosphoramides, particularly (137) and proceed with good to high enantioselectivity with achiral enolates and aldehydes (Scheme 34). ... 

The reductive coupling of ketones or aldehydes with electrophilic alkenes such as conjugated esters (Scheme 52) has been described independently by Inanaga et al. [38] and Fukuzawa et al. [123,124]. The reaction was performed in THF either in the presence of HMPA [38] or an alcohol [123,124]. The mechanistic aspects of this reaction have been discussed [ 124]. Presumably, the ketyl radical or its protonated form adds to ethyl acrylate with formation of the C-C bond. An efficient enantioselective synthesis of v-butyrolactones has been derived by using AT-methylephedrinyl acrylate or crotonate [125]. One example (synthesis of 33) is indicated in Scheme 52. 

The short preparative review presented here - without any consideration of mechanistic aspects - has hopefully demonstrated why we consider the TADDOL system a candidate for a universally applicable chiral auxiliary. It has all the features, first of all the synthetic availability and almost unhm-ited flexibility to be used not only for all types of enantioselective syntheses and resolutions (to prepare enantiomerically pure compounds, EPC [86] [87]),... 

A multicomponent bifunctional catalytic system based on a titanium complex was also used for the efficient enantioselective cyanation of aldehydes with ethyl cyanoformate [221]. The catalyst was readily prepared by the reaction of Ti(O Pr)4 with (S)-6,6 -Br2BINOL in combination with cinchonine and (lR,2S)-(—)-N-methylephedrine. As shown in Scheme 14.91, the optimized catalyst combination (10 mol%) promotes the reaction smoothly to afford the desired cyanohydrins ethyl carbonates in moderate to excellent isolated yields (up to 95%) with high enantioselectivities (up to 94% ee). Although the mechanistic aspects... 

These findings led to elucidation of the mechanistic aspects of Upase (Novozym 435) catalysis enantioselection is operated by the deacylation step as shown in Fig. 3 [53], where only dimer formation is shown for simphcity. It is well accepted that at first the monomer (substrate) is activated by enzyme with formatimi of an (/ )-acyl-enzyme intermediate (enzyme-activated monomer, EM) [ acylation of lipase step (a) in Fig. 3]. Onto the activated carlxMiyl carbon of EM, the OH group of the D-lactate nucleophUically attacks to form an ester bond, liberating Upase enzyme and giving rise to D,D-dimer [ deacylation of Upase step (b) in Fig. 3]. 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

Herein we provide insight into their extremely high substrate selectivity and explore in detail aspects like regioselectivity, diasteroselectivity, and enantioselectivity in the oxidation of a wide range of substrates. Further details into the selectivity of this catalyst are provided by a mechanistic investigation performed employing the so-called "reaction progress kinetic analysis" approach recently developed by Blackmond [33]. 

One of the most fascinating aspects in the history of asymmetric catalysis with its countless successful applications in the stereoselective synthesis of a broad variety of functional groups is the structural variety of the complexes which are able to be used as catalysts [1,2]. Many catalysts have been developed based on different ideas and concepts of mechanistic effect. However, in spite of the abundance of such catalysts which have been successfully applied in asymmetric catalysis, not a handful of them possess multifunctional abilities catalyzing different type of enantioselective reactions. The development of such a type of chiral catalyst, the catalytic effect of which is not limited to one reaction but to different types of asymmetric synthetic organic transformations, remained an attractive challenge for a long time. 

Finally, stereochemical aspects of the mechanism have been extensively studied by Evans and coworkers during their construction of a model to map the diastereoselective induction observed in the course of the aldol reaction. Similarly, mechanistic studies were performed by the Evans group with regards to their bis(oxazolinyl)-pyridine (pybox)-copper(II) complex, a catalyst for the enantioselective Mukaiyama reaction. ... 

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